Pain
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Randomized Controlled Trial
Cebranopadol, a novel first-in-class analgesic drug candidate: first experience in patients with chronic low back pain in a randomized clinical trial.
Chronic low back pain (LBP) is a common condition, usually with the involvement of nociceptive and neuropathic pain components, high economic burden and impact on quality of life. Cebranopadol is a potent, first-in-class drug candidate with a novel mechanistic approach, combining nociceptin/orphanin FQ peptide and opioid peptide receptor agonism. We conducted the first phase II, randomized, double-blind, placebo- and active-controlled trial, evaluating the analgesic efficacy, safety, and tolerability of cebranopadol in patients with moderate-to-severe chronic LBP with and without neuropathic pain component. ⋯ Those patients reaching the target doses had an acceptable tolerability profile. The incidence rate of most frequently reported treatment-emergent adverse events during maintenance phase was ≤10%. Although further optimizing the titration scheme to the optimal dose for individual patients is essential, cebranopadol is a new drug candidate with a novel mechanistic approach for potential chronic LBP treatment.
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Randomized Controlled Trial
The effect of a lay-led, group-based self-management program for patients with chronic pain: a randomized controlled trial of the Danish version of the Chronic Pain Self-Management Programme.
The Stanford Chronic Pain Self-Management Programme (CPSMP) consists of 6 2½-hour weekly workshops focusing on how to manage pain in daily life. The workshops are facilitated by 2 workshop leaders of whom at least 1 must suffer from a long-term pain condition. The program is highly structured and manualized. ⋯ Small positive effects on emotional distress and illness worry 3 months after CPSMP were observed. Lay-led CPSMP is not recommended as treatment for chronic pain-related disability. This heterogeneous group of patients with pain did not benefit from the CPSMP except for a small, but clinically insignificant improvement in psychological well-being.
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Randomized Controlled Trial
Midazolam as an active placebo in three fentanyl-validated nociceptive pain models.
The use of inactive placebos in early translational trials of potentially analgesic compounds is discouraged because of the side-effect profiles of centrally acting analgesics. Therefore, benzodiazepines are used, although their use has not been validated in this context. Whether benzodiazepines confound the results of acute pain tests is unknown. ⋯ The findings of this study show that midazolam can be used as an active placebo in analgesic drug trials. Furthermore, the proposed models were simple to implement and very effective in detecting analgesia. The test battery can be used in translational trials for new compounds and comes with an active placebo and an optional active comparator.
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Randomized Controlled Trial
Side effects can enhance treatment response through expectancy effects: an experimental analgesic randomized controlled trial.
In randomized controlled trials, medication side effects may lead to beliefs that one is receiving the active intervention and enhance active treatment responses, thereby increasing drug-placebo differences. We tested these hypotheses with an experimental double-blind randomized controlled trial of a nonsteroidal anti-inflammatory drug with and without the addition of atropine to induce side effects. One hundred healthy volunteers were told they would be randomized to either combined analgesics that might produce dry mouth or inert placebos. ⋯ A chain of mediation analysis demonstrated that the addition of atropine increased dry mouth symptoms, which increased beliefs that one had received the active medication, which, in turn, increased analgesia. In addition to this indirect effect of atropine on analgesia (via dry mouth and beliefs), analyses suggest that among those who received diclofenac, atropine directly increased analgesia. This possible synergistic effect between diclofenac and atropine might warrant future research.
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Randomized Controlled Trial
Economic evaluation of an implementation strategy for the management of low back pain in general practice.
In connection with the publication of a clinical practice guideline on the management of low back pain (LBP) in general practice in Denmark, a cluster randomised controlled trial was conducted. In this trial, a multifaceted guideline implementation strategy to improve general practitioners' treatment of patients with LBP was compared with a usual implementation strategy. The aim was to determine whether the multifaceted strategy was cost effective, as compared with the usual implementation strategy. ⋯ Sensitivity analyses showed that results were sensitive to uncertainty. In conclusion, the multifaceted implementation strategy was cost saving when compared with the usual strategy for implementing LBP clinical practice guidelines in general practice. Furthermore, there was no significant difference in effect, and the estimate was sensitive to uncertainty.